Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) interactions with TNF superfamily (TNFSF) ligands (TNFL) control key cellular processes such as differentiation, proliferation, apoptosis, and cell growth. Dysregulation of these pathways has been shown to result in a wide range of pathological conditions, including autoimmune diseases, inflammation, cancer, and viral infection. There are 29 very diverse family members of TNFRSF reported in humans: 22 are type I transmembrane receptors (single pass with the N terminus on extracellular side of the cell membrane) and have a clear signal peptide; the remaining 7 members are either type III transmembrane receptors (single pass with the N terminus on extracellular side of the membrane but no signal sequence; TNFR13B, TNFR13C, TNFR17, and XEDAR), or attached to the membrane via a glycosylphosphatidylinositol (GPI) linker (TNFR10C), or secreted as soluble receptors (TNFR11B and TNFR6B). All TNFRs contain relatively short cysteine-rich domains (CRDs) in the ectodomain, and are involved in interaction with the TNF homology domain (THD) of their ligands. TNFRs often have multiple CRDs (between one and six), with the most frequent configurations of three or four copies; most CRDs possess three disulfide bridges, but could have between one and four. Localized or genome-wide duplication and evolution of the TNFRSF members appear to have paralleled the emergence of the adaptive immune system; teleosts (i.e. ray-finned, bony fish), which possess an immune system with B and T cells, possess primary and secondary lymphoid organs, and are capable of adaptive responses to pathogens also display several characteristics that are different from the mammalian immune system, making teleost TNFSF orthologs and paralogs of interest to better understand immune system evolution and the immunological pathways elicited to pathogens.

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gi 16306481 146 SALPRHSVPVPATELGSTELVTTKT 170
Cdd:cd13414 136 KADSDHFFPLPAMEEGATILVTTKT 160

Tumor necrosis factor receptor superfamily member 17 (TNFRSF17), also known as B cell maturation antigen (BCMA), as well as TNFRSF13A; TNFRSF17 (also known as TNFRSF13A, B cell maturation antigen or BCMA, CD269) is predominantly expressed on terminally differentiated B cells, including multiple myeloma cells, and is important for B cell development and autoimmune response. Upon binding to its ligands, B cell activator of the TNF family (BAFF, also known as TNSF13B, TALL-1, BLyS, zTNF4), and a proliferation inducing ligand (APRIL), BCMA activates NF-kappaB and MAPK8/JNK; it has a higher affinity for APRIL than for BAFF. This receptor may transduce signals for cell survival and proliferation by binding to TRAF1, TRAF2, and TRAF3. BCMA expression has also been linked to a number of cancers, autoimmune disorders, and infectious diseases. It has been shown that although BCMA does not play a role in normal B cell homeostasis, it is critical for the long-term survival of bone marrow plasma cells. BCMA is expressed in a number of hematologic malignancies, including both Hodgkin's and non-Hodgkin's lymphomas, as well as primary tumor cells and cell lines of multiple myeloma, playing a critical role in protecting myeloma cells from apoptosis. BCMA has been identified as a promising chimeric antigen receptor (CAR) target for multiple myeloma; CARs are synthetic transmembrane proteins used to redirect autologous T cells with a new specificity for antigens on the surface of cancer cells. BCMA may also be implicated in the context of both viral and fungal infections; peripheral blood B cells isolated from HIV+ viremic patients have increased expression levels of BCMA, and significant decreased levels are found during fungal infection with C. neoformans. BCMA has been linked to mucosal immunity; its signaling in B cells and non-B cells is important for driving protective IgA responses. Also, abnormal expression or signaling of BCMA in the gut may be relevant to diseases, such as irritable bowel disease and ulcerative colitis.

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                ....*....|....*....|....*
gi 16306481 146 SALPRHSVPVPATELGSTELVTTKT 170
Cdd:cd13414 136 KADSDHFFPLPAMEEGATILVTTKT 160

Tumor necrosis factor receptor superfamily member 17 (TNFRSF17), also known as B cell maturation antigen (BCMA), as well as TNFRSF13A; TNFRSF17 (also known as TNFRSF13A, B cell maturation antigen or BCMA, CD269) is predominantly expressed on terminally differentiated B cells, including multiple myeloma cells, and is important for B cell development and autoimmune response. Upon binding to its ligands, B cell activator of the TNF family (BAFF, also known as TNSF13B, TALL-1, BLyS, zTNF4), and a proliferation inducing ligand (APRIL), BCMA activates NF-kappaB and MAPK8/JNK; it has a higher affinity for APRIL than for BAFF. This receptor may transduce signals for cell survival and proliferation by binding to TRAF1, TRAF2, and TRAF3. BCMA expression has also been linked to a number of cancers, autoimmune disorders, and infectious diseases. It has been shown that although BCMA does not play a role in normal B cell homeostasis, it is critical for the long-term survival of bone marrow plasma cells. BCMA is expressed in a number of hematologic malignancies, including both Hodgkin's and non-Hodgkin's lymphomas, as well as primary tumor cells and cell lines of multiple myeloma, playing a critical role in protecting myeloma cells from apoptosis. BCMA has been identified as a promising chimeric antigen receptor (CAR) target for multiple myeloma; CARs are synthetic transmembrane proteins used to redirect autologous T cells with a new specificity for antigens on the surface of cancer cells. BCMA may also be implicated in the context of both viral and fungal infections; peripheral blood B cells isolated from HIV+ viremic patients have increased expression levels of BCMA, and significant decreased levels are found during fungal infection with C. neoformans. BCMA has been linked to mucosal immunity; its signaling in B cells and non-B cells is important for driving protective IgA responses. Also, abnormal expression or signaling of BCMA in the gut may be relevant to diseases, such as irritable bowel disease and ulcerative colitis.

                        10        20
                ....*....|....*....|....*
gi 16306481 146 SALPRHSVPVPATELGSTELVTTKT 170
Cdd:cd13414 136 KADSDHFFPLPAMEEGATILVTTKT 160